2022
Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer
Adua S, Arnal-Estapé A, Zhao M, Qi B, Liu Z, Kravitz C, Hulme H, Strittmatter N, López-Giráldez F, Chande S, Albert A, Melnick M, Hu B, Politi K, Chiang V, Colclough N, Goodwin R, Cross D, Smith P, Nguyen D. Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer. Nature Communications 2022, 13: 7690. PMID: 36509758, PMCID: PMC9744876, DOI: 10.1038/s41467-022-34889-z.Peer-Reviewed Original ResearchConceptsGene expression programsRas homolog family member ACancer cellsFamily member AEpidermal growth factor receptorExpression programsMetastatic cancer cellsSRF signalingGrowth factor receptorTumor microenvironmentLung cancerFunctional linkExtracellular lamininDrug-resistant cancer cellsMutant non-small cell lung cancerNon-small cell lung cancerCentral nervous system relapseMolecular studiesMember AEGFR-mutant lung cancerFactor receptorNervous system relapseCell lung cancerDisseminated tumor cellsBrain tumor microenvironmentHuman WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation
Cai WL, Chen JF, Chen H, Wingrove E, Kurley SJ, Chan LH, Zhang M, Arnal-Estape A, Zhao M, Balabaki A, Li W, Yu X, Krop ED, Dou Y, Liu Y, Jin J, Westbrook TF, Nguyen DX, Yan Q. Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation. ELife 2022, 11: e78163. PMID: 36043466, PMCID: PMC9584608, DOI: 10.7554/elife.78163.Peer-Reviewed Original ResearchConceptsBreast cancer cellsMetastatic breast cancerBreast cancerRibosomal gene expressionCancer cellsKnockdown of WDR5Vivo genetic screenReversible epigenetic mechanismsGenetic screenTranslation regulationTriple-negative breast cancerEpigenetic regulatorsEpigenetic mechanismsBreast cancer growthCancer-related deathTranslation efficiencyWDR5Novel therapeutic strategiesTranslation rateGene expressionCell growthAdvanced diseaseEffective therapyMetastatic capabilityPotent suppression
2019
Adaptive Protein Translation by the Integrated Stress Response Maintains the Proliferative and Migratory Capacity of Lung Adenocarcinoma Cells
Albert AE, Adua SJ, Cai WL, Arnal-Estapé A, Cline GW, Liu Z, Zhao M, Cao PD, Mariappan M, Nguyen DX. Adaptive Protein Translation by the Integrated Stress Response Maintains the Proliferative and Migratory Capacity of Lung Adenocarcinoma Cells. Molecular Cancer Research 2019, 17: 2343-2355. PMID: 31551255, PMCID: PMC6938689, DOI: 10.1158/1541-7786.mcr-19-0245.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 4Adenocarcinoma of LungAmino AcidsCarbon-Nitrogen Ligases with Glutamine as Amide-N-DonorCell Line, TumorCell ProliferationCyclin B1Eukaryotic Initiation Factor-2Gene Expression Regulation, NeoplasticHumansNF-E2-Related Factor 2Oxidative StressPhosphatidylinositol 3-KinasesProtein BiosynthesisProteostasisSignal TransductionStress, PhysiologicalTOR Serine-Threonine KinasesConceptsIntegrated stress responseProtein translationCell cycle progressionLung adenocarcinoma cellsLung cancer cellsNew regulatory layerCertain oncogenic mutationsAmino acid limitationNovel regulatory mechanismControl of proteostasisCancer cellsDifferent biological consequencesEIF2α-dependent mannerAmino acid metabolismAdenocarcinoma cellsNrf2 protein levelsPI3K pathwayConserved pathwayRegulatory layerISR pathwayATF4 branchCell cycle regulator cyclin B1MTOR/PI3K pathwaySelect proteinsAsparagine synthetase
2018
Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment.
Stevens LE, Arnal-Estapé A, Nguyen DX. Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment. Journal Of Visualized Experiments 2018 PMID: 30010648, PMCID: PMC6102009, DOI: 10.3791/56650.Peer-Reviewed Original ResearchConceptsCancer cell engraftmentAirways of miceLung cancer cellsCell engraftmentLung cancerTumor cellsTumorigenic capacityNew orthotopic modelNon-physiological sitesTumor cell injectionCancer cellsLung tumor incidenceTreatment-refractory diseaseFull clinical spectrumLung cancer subtypesLung adenocarcinoma subtypesAdditional animal modelsStrains of miceFlanks of miceRefractory diseaseThoracic malignanciesAdenocarcinoma subtypeClinical spectrumOrthotopic transplantationTumor incidence
2017
Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases
Stevens LE, Cheung WKC, Adua SJ, Arnal-Estapé A, Zhao M, Liu Z, Brewer K, Herbst RS, Nguyen DX. Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases. Cancer Research 2017, 77: 1905-1917. PMID: 28196904, PMCID: PMC5468792, DOI: 10.1158/0008-5472.can-16-1978.Peer-Reviewed Original ResearchConceptsBrain metastatic nicheRisk of relapseDistant metastasisPoor prognosisLUAD subtypesLung tumorsLung adenocarcinomaLUAD cellsMetastatic outgrowthMetastatic nicheCancer ResCancer cellsECM-mediated signalingExtracellular matrix moleculesCell survivalMolecular signaturesDifferential expressionHMMRMatrix moleculesImportant mechanismCellsRelapseAdenocarcinomaPrognosisMetastasis
2015
Enhanced MAF Oncogene Expression and Breast Cancer Bone Metastasis
Pavlovic M, Arnal-Estapé A, Rojo F, Bellmunt A, Tarragona M, Guiu M, Planet E, Garcia-Albéniz X, Morales M, Urosevic J, Gawrzak S, Rovira A, Prat A, Nonell L, Lluch A, Jean-Mairet J, Coleman R, Albanell J, Gomis R. Enhanced MAF Oncogene Expression and Breast Cancer Bone Metastasis. Journal Of The National Cancer Institute 2015, 107: djv256. PMID: 26376684, PMCID: PMC4681582, DOI: 10.1093/jnci/djv256.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorBone NeoplasmsBreast NeoplasmsCell Line, TumorDNA Copy Number VariationsFemaleGene Expression Regulation, NeoplasticHeterograftsHumansImmunohistochemistryIn Situ Hybridization, FluorescenceIncidenceMiceMice, Inbred BALB COdds RatioPredictive Value of TestsPrognosisProportional Hazards ModelsProto-Oncogene Proteins c-mafUp-RegulationConceptsBreast cancer bone metastasisCopy number aberrationsCancer bone metastasisBone metastasesRisk of bone metastasisAssociated with bone metastasisBreast cancer cells in vivoPrimary breast tumorsBreast cancer patient populationCancer cells in vivoMetastasis to boneClinical follow-upBreast cancer cellsAssociated with riskCells in vivoCancer patient populationBone relapseCause-specific hazard modelBreast tumorsFollow-upMAF overexpressionMetastasisPatient populationProtein overexpressionCancer cellsNeural Regulation of Hematopoiesis, Inflammation, and Cancer
Hanoun M, Maryanovich M, Arnal-Estapé A, Frenette P. Neural Regulation of Hematopoiesis, Inflammation, and Cancer. Neuron 2015, 86: 360-373. PMID: 25905810, PMCID: PMC4416657, DOI: 10.1016/j.neuron.2015.01.026.Peer-Reviewed Original ResearchConceptsAutonomic nervous systemStem cell niche homeostasisRegulation of hematopoiesisStromal constituentsHematopoietic homeostasisHematopoietic systemTherapeutic strategiesInflammatory responseNiche homeostasisCancer cellsNeural regulationFlight-or-fight responsePeripheral innervationNervous systemCancerNeural circuitryRegulate cell behaviorInflammationHomeostasisCell behaviorHematopoiesisInnervationResponseMicroenvironmentSweets for a Bitter End: Lung Cancer Cell–Surface Protein Glycosylation Mediates Metastatic Colonization
Arnal-Estapé A, Nguyen DX. Sweets for a Bitter End: Lung Cancer Cell–Surface Protein Glycosylation Mediates Metastatic Colonization. Cancer Discovery 2015, 5: 109-111. PMID: 25656895, PMCID: PMC4340588, DOI: 10.1158/2159-8290.cd-15-0013.Peer-Reviewed Original Research
2012
Identification of NOG as a Specific Breast Cancer Bone Metastasis-supporting Gene* ♦
Tarragona M, Pavlovic M, Arnal-Estapé A, Urosevic J, Morales M, Guiu M, Planet E, González-Suárez E, Gomis R. Identification of NOG as a Specific Breast Cancer Bone Metastasis-supporting Gene* ♦. Journal Of Biological Chemistry 2012, 287: 21346-21355. PMID: 22547073, PMCID: PMC3375555, DOI: 10.1074/jbc.m112.355834.Peer-Reviewed Original ResearchConceptsBreast cancer cellsCancer cellsPrimary siteNOG expressionBone metastatic potentialBone metastatic lesionsMetastatic breast cancer cellsHuman breast cancer cellsAggressive cancer cellsBone relapseMetastatic lesionsPrimary tumorMetastatic nicheTumor cellsBone colonizationMetastatic potentialDistant organsMetastasisOsteoclast differentiationColonic functionBone degradationCell functionNOGBMP inhibitorsBoneEpithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells
Celià-Terrassa T, Meca-Cortés Ó, Mateo F, de Paz A, Rubio N, Arnal-Estapé A, Ell B, Bermudo R, Díaz A, Guerra-Rebollo M, Lozano J, Estarás C, Ulloa C, ρlvarez-Simón D, Milà J, Vilella R, Paciucci R, Martínez-Balbás M, de Herreros A, Gomis R, Kang Y, Blanco J, Fernández P, Thomson T. Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells. Journal Of Clinical Investigation 2012, 122: 1849-1868. PMID: 22505459, PMCID: PMC3366719, DOI: 10.1172/jci59218.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, DifferentiationCadherinsCell Line, TumorCell MovementCell ShapeCoculture TechniquesEpithelial CellsEpithelial-Mesenchymal TransitionGene Expression ProfilingGene Regulatory NetworksHomeodomain ProteinsHumansMaleMiceMice, Inbred NODMice, SCIDNeoplasm InvasivenessNeoplasm MetastasisNeoplasm StagingNeoplasm TransplantationProstatic NeoplasmsRepressor ProteinsSnail Family Transcription FactorsSpheroids, CellularTranscription FactorsTwist-Related Protein 1Urinary Bladder NeoplasmsZinc Finger E-box-Binding Homeobox 1ConceptsEpithelial-mesenchymal transitionDistant metastasisSelf-renewalGene programTumor-initiating cellsEpithelial-mesenchymal transition programProstate cancer cellsIn vitro invasionPrimary implantation sitesHuman cellular modelsMetastatic populationBladder cancerTumor subpopulationsLocal invasionMesenchymal-likeEpithelial featuresMetastatic phenotypeNeoplastic cellsMalignant progressionImplantation sitesMesenchymal traitsEMT factorsCancer cellsMesenchymal genesIn vivo
2010
HER2 Silences Tumor Suppression in Breast Cancer Cells by Switching Expression of C/EBPβ Isoforms
Arnal-Estapé A, Tarragona M, Morales M, Guiu M, Nadal C, Massagué J, Gomis R. HER2 Silences Tumor Suppression in Breast Cancer Cells by Switching Expression of C/EBPβ Isoforms. Cancer Research 2010, 70: 9927-9936. PMID: 21098707, DOI: 10.1158/0008-5472.can-10-0869.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBlotting, WesternBreast NeoplasmsCCAAT-Enhancer-Binding Protein-betaCell LineCell Line, TumorCellular SenescenceGene Expression Regulation, NeoplasticHumansIn Situ Hybridization, FluorescenceMiceMice, NudePhosphorylationPromoter Regions, GeneticProtein BindingProtein BiosynthesisProtein IsoformsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mycReceptor, ErbB-2Reverse Transcriptase Polymerase Chain ReactionRNA InterferenceTransforming Growth Factor betaTrastuzumabConceptsBreast cancer cellsTumor suppressionBreast cancerOncogene-induced senescenceCancer cellsHER2-overexpressing breast cancer cellsSubtypes of breast cancerHER2 antibody trastuzumabTransforming growth factor-bBreast cancer developmentGrowth factor BTranscriptional repressor complexHER2 signalingSuppressor responseTumor progressionMammary epithelial cellsAntibody trastuzumabHER2Cancer developmentEpithelial cellsSuppressor functionSwitching expressionInterfere with activitiesMYC promoterBreast